The mechanism of exercise-induced increase in muscle insulin sensitivity

2010 Fiscal Year Final Research Report

• Project/Area Number: 21700702
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: IKEDA Shin-ichi Juntendo University, 医学(系)研究科, 研究員 (50534898)
• Project Period (FY): 2009 – 2010
• Keywords: 運動 / インスリン感受性 / マクロファージ

Research Abstract

Type 2 diabetes and obesity are characterized by insulin resistance in skeletal muscle. It has been well demonstrated that exercise increase insulin sensitivity in skeletal muscle. However, it remains still unclear how a single bout exercise enhance subsequent insulin sensitivity. Recently, it has been reported that macrophages, at least partly, regulate insulin sensitivity in several insulin target organs. We, therefore, hypothesized that macrophages are involved in the mechanisms of exercise-induced enhancement of insulin sensitivity in skeletal muscle. To test this hypothesis, we injected saline (SAL) or clodronate liposome (CL), a macrophage suppressor, to C57BL6J mice. Then, mice were subjected to a single bout of treadmill running. Twenty-four hour after exercise, we measured ex-vivo insulin-stimulated 2-deoxy glucose (DG) uptake in skeletal muscle. We observed that a single bout exercise enhanced macrophage accumulation and insulin-stimulated 2-DG uptake in plantaris muscle in SAL group. However, CL treatment completely abolished these changes. We also observed that phosphorylation state of Akt, AS160 and AMPK were not changed by CL treatment. From these results, we conclude that macrophages are involved in the mechanisms of exercise-induced enhancement of insulin sensitivity in skeletal muscle, independent of Akt and AMPK phosphorylation states.

Research Products

• [Journal Article] Determinants of intramyocellular lipid accumulation after dietary fat loading in non-obese men
  • Author(s): Sakurai Y, Tamura Y, Takeno K, Kumashiro N, Sato F, Kakehi S, Ikeda S, Katamoto S, Ogura Y, Saga N, Naito H, Fujitani Y, Hirose T, Kawamori R, Watada H
  • Journal Title: J Diabetes Invest In press
• [Presentation] 筋サイズ並びに筋糖代謝に対するPKCδの関与の検討 (2010)
  • Author(s): 池田真一、田村好史、筧佐織、河盛隆造、綿田裕孝
  • Organizer: 第65回日本体力医学会大会
  • Place of Presentation: ポスター
  • Year and Date: 20100900
• [Presentation] 脂肪負荷感受性の規定因子の解明 (2010)
  • Author(s): 筧佐織、田村好史、池田真一、綿田裕孝、河盛隆造
  • Organizer: 第65回日本体力医学会
  • Place of Presentation: ポスター
  • Year and Date: 20100900
• [Presentation] Autophagy is involved in slow skeletal muscle atrophy (2010)
  • Author(s): Norihiko Furuya, Shin-ichi Ikeda, Junji Ezaki, Masaaki Komatsu, Eiki Kominami, Takashi Ueno
  • Organizer: 第62回日本細胞生物学会大会,口頭
  • Year and Date: 20100500
• [Presentation] Susceptible Factors for Intramyocellular Lipid Accumulation by Dietary Fat Loading in Non-Obese Men. (2010)
  • Author(s): Sakurai Y, Tamura Y, Takeno K, Kumashiro N, Sato F, Ikeda S, Kakehi S, Katamoto S, Naito H, Saga N, Ogura Y, Hirose T, Fujitani Y, Watada H
  • Organizer: American Diabetes Association 70^<th> Scientific sessions. Orlando
  • Year and Date: 20100000
• [Presentation] ヒトにおける高脂肪食負荷が、骨格筋細胞内脂質蓄積とインスリン抵抗性発症に与える影響とその規定因子 (2009)
  • Author(s): 櫻井裕子, 田村好史, 竹野景海, 熊代尚記, 池田真一, 筧佐織, 綿田裕孝, 河盛隆造
  • Organizer: 第52回日本糠尿病学会年次学術集会p. S-161
  • Place of Presentation: 大阪府大阪市(日本)
  • Year and Date: 20090000
• [Presentation] ヒトにおける高脂肪食負荷が、骨格筋細胞内脂質蓄積とインスリン抵抗性発症に与える影響とその規因子 (2009)
  • Author(s): 田村好史, 櫻井裕子, 竹野景海, 熊代尚記, 池田真一, 筧佐織, 綿田裕孝, 河盛隆造
  • Organizer: 第59回日本体質医学会総会東京都千代田区(日本)
  • Place of Presentation: 日本体質医学会
  • Year and Date: 20090000
• [Presentation] Effects of high fat diet on intramyocellular lipid and insulin resistance. (2009)
  • Author(s): Tamura Y, Sakurai Y, Takeno K, Kumashiro N, Ikeda S, Kakehi S, Watada H, Kawamori R
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090000
• [Presentation] Effects of high fat diet on intramyocellular lipid and insulin resistance. (2009)
  • Author(s): Sakurai Y, Tamura Y, Takeno K, Kumashiro N, Ikeda S, Kakehi S, Watada H, Kawamori R
  • Organizer: The First Asia-Pacific Conference on Health Promotion and Education
  • Place of Presentation: Chiba, Japan
  • Year and Date: 20090000
• [Presentation] Diabetes and Exercise : Intramycellular Lipid Accumulation and Insulin Sensitivity. (2009)
  • Author(s): Tamura Y, Sakurai Y, Takeno K, Kakehi S, Ikeda S, Sato F, Hirose T, Watada H, Kawamori R.
  • Organizer: In The 15th Korea-Japan Symposium on Diabetes Mellitus Jeju p.84-85
  • Place of Presentation: Korea
  • Year and Date: 20090000
• [Presentation] 第64回日本体力医学会 (2009)
  • Author(s): 池田真一、田村好史、筧佐織、綿田裕孝、河盛隆造
  • Organizer: 廃用性筋萎縮に対するPKCδの関与の検討
  • Place of Presentation: ポスター
  • Year and Date: 2009-09-20
• [Presentation] 第64回日本体力医学会 (2009)
  • Author(s): 筧佐織、田村好史、池田真一、綿田裕孝、河盛隆造
  • Organizer: 筋インスリン抵抗性に対する高脂肪食と身体活動量の作用
  • Place of Presentation: ポスター
  • Year and Date: 2009-09-19
• [Presentation] 第64回日本体力医学会 (2009)
  • Author(s): 田村好史、櫻井裕子、筧佐織、池田真一、佐賀典生、小倉裕司、内藤久士、綿田裕孝、河盛隆造
  • Organizer: ヒトにおける高脂肪食負荷が、骨格筋細胞内脂質蓄積とインスリン抵抗性発生に与える影響とその規定因子,口頭
  • Year and Date: 2009-09-18
• [Presentation] 異所性脂肪蓄積とインスリン抵抗性
  • Author(s): 田村好史, 櫻井裕子, 竹野景海, 筧佐織, 池田真一, 川口美奈子, 渡邉隆宏, 佐藤文彦, 河盛隆造, 綿田裕孝
  • Organizer: Advans研究会、口頭、12月
• [Presentation] 骨格筋萎縮過程におけるオートファジーの役割
  • Author(s): 古屋徳彦、池田真一、江崎淳二、小松雅明、木南英紀、上野隆
  • Organizer: 特定領域「タンパク質分解」班会議、口頭、11月
• [Presentation] ヒトにおける高脂肪食負荷が骨格筋細胞内脂質蓄積とインスリン感受性に与える影響とその規定因子の解明
  • Author(s): 櫻井裕子, 田村好史, 竹野景海, 熊代尚紀, 佐藤文彦, 池田真一, 筧佐織, 形本静夫, 内藤久士, 小倉裕司, 佐賀典生, 弘世貴久, 綿田裕孝, 河盛隆造
  • Organizer: 第53回日本糖尿病学会年次学術集会、口頭、5月
• [Book] 光るクラゲがノーベル賞をとった理由(日本評論者)
  • Publisher: 生化学若い研究者の会(共著)
• [Book] 肝インスリン抵抗性発症におけるPGC-1αの意義(科学評論者)
  • Author(s): 池田真一、田村好史、綿田裕孝
• [Remarks] ホームページ等